CD146 expression on primary nonhematopoietic bone marrow stem cells is correlated with in situ localization

CD146 expression on primary nonhematopoietic bone marrow stem cells is correlated with in situ localization
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DOI:
10.1182/blood-2010-08-304287
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发表时间:
2011-05-12
期刊:
影响因子:
20.3
通讯作者:
Scheding, Stefan
Scheding, Stefan
中科院分区:
医学1区
文献类型:
--
作者:
Tormin, Ariane;Li, Ou;Scheding, Stefan

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非造血骨髓间充质干细胞(BM-MSCs)是骨髓基质和造血环境的核心重要性。然而,骨髓中特定MSC群体的确切表型和解剖学分布尚不清楚。我们对原代人BM-MSCs的表型进行了表征,发现所有可测定的集落形成单位-成纤维细胞(CFU-Fs)不仅高度且排他性地富集在lin(-)/CD 271(+)/CD 45(-)/CD 146(+)干细胞组分中,而且还高度且排他性地富集在lin(-)/CD 271(+)/CD 45(-)/CD 146(-/low)细胞中。无论CD 146表达如何,这两个群体都具有相似的表型和基因型,产生典型的培养基质细胞,并在体内形成骨和造血基质。有趣的是,CD 146在常氧下上调,在缺氧下下调。这与原位定位差异相关,共表达CD 146的网状细胞位于血管周围区域,而骨衬MSC仅表达CD 271。在这两个区域,CD 34(+)造血干/祖细胞位于接近MSC。这些新的发现表明,CD 146的表达区分血管周围与骨内膜定位的非造血BM-MSC群体,这可能是有用的造血环境的研究。(血。2011; 117(19):5067-5077)
Nonhematopoietic bone marrow mesenchymal stem cells (BM-MSCs) are of central importance for bone marrow stroma and the hematopoietic environment. However, the exact phenotype and anatomical distribution of specified MSC populations in the marrow are unknown. We characterized the phenotype of primary human BM-MSCs and found that all assayable colony-forming units-fibroblast (CFU-Fs) were highly and exclusively enriched not only in the lin(-)/CD271(+)/CD45(-)/CD146(+) stem-cell fraction, but also in lin(-)/CD271(+)/CD45(-)/CD146(-/low) cells. Both populations, regardless of CD146 expression, shared a similar phenotype and genotype, gave rise to typical cultured stromal cells, and formed bone and hematopoietic stroma in vivo. Interestingly, CD146 was up-regulated in normoxia and down-regulated in hypoxia. This was correlated with in situ localization differences, with CD146 coexpressing reticular cells located in perivascular regions, whereas bone-lining MSCs expressed CD271 alone. In both regions, CD34(+) hematopoietic stem/progenitor cells were located in close proximity to MSCs. These novel findings show that the expression of CD146 differentiates between perivascular versus endosteal localization of non-hematopoietic BM-MSC populations, which may be useful for the study of the hematopoietic environment. (Blood. 2011; 117(19): 5067-5077)